A Phase III trial (NCT03257267) evaluating Libtayo? (cemiplimab) as a monotherapy in advanced cervical cancer has been stopped early after the treatment was found to reduce risk of death by 31 percent compared to chemotherapy. Libtayo is a PD-1 inhibitor that has now shown promise in four different cancer types.

The open-label, randomised, multi-centre, Phase III trial investigated Libtayo monotherapy versus an investigator’s choice of chemotherapy in patients with recurrent or metastatic cervical cancer that has progressed on platinum-based chemotherapy. Patients were allowed to enrol regardless of PD-L1 expression status, with 78 percent of patients having squamous cell carcinoma and 22 percent having adenocarcinoma.

The trial will be stopped early based on a unanimous recommendation by the Independent Data Monitoring Committee (IDMC) and the data will form the basis of regulatory submissions in 2021.

“Libtayo monotherapy is the first medicine to demonstrate an improvement in overall survival in women with recurrent or metastatic cervical cancer following progression on platinum-based chemotherapy in a Phase III trial,” said Dr Krishnansu Tewari, Professor and Director of the Division of Gynecologic Oncology at the University of California, Irvine, US, and a trial investigator. “This landmark clinical achievement will bring hope to women with advanced cervical cancer who are often younger than patients with other cancers. This is reflected in this trial where the average age was 51.”

In the trial patients were randomised to receive Libtayo monotherapy (350mg every three weeks) or an investigator’s choice of commonly used chemotherapy (pemetrexed, vinorelbine, topotecan, irinotecan or gemcitabine). Libtayo was shown to reduce risk of death overall by 31 percent compared to chemotherapy, with median overall survival increased from 8.5 moths to 12 months with the PD-L1 inhibitor. In patients with squamous cell carcinoma, patients on Libtayo were 27 percent less likely to die (median survival 11.1 months versus 8.8 months with chemo). Those taking Libtayo with adenocarcinoma were 44 percent less likely to die, compared to chemotherapy patients (median survival 13.3 months versus seven months, respectively).

Overall survival was the primary endpoint of the study, when the IDMC reviewed the data per a protocol-specified interim analysis, it recommended stopping the trial. Detailed results will be presented at an upcoming medical meeting.

No new Libtayo safety signals were observed. Safety was assessed in patients who received at least one dose of study treatment: 300 patients in the Libtayo group (median duration of exposure was 15 weeks) and 290 patients in the chemotherapy group (median duration of exposure was 10 weeks). Adverse events (AEs) were observed in 88 percent of Libtayo patients and 91 percent of chemotherapy patients, with serious AEs occurring in 30 percent of Libtayo patients and 27 percent of chemotherapy patients. AEs that occurred more often in the Libtayo group and in at least 10 percent of patients were fatigue (17 percent Libtayo, 16 percent chemo), urinary tract infections (12 versus nine percent), back pain (11 versus nine percent) and arthralgia (10 versus three percent). Discontinuations due to AEs occurred in eight percent of Libtayo patients and five percent of chemotherapy patients.

“Recurrent or metastatic cervical cancer is notoriously difficult to treat and has no approved standard of care after first-line chemotherapy,” commented Dr Israel Lowy, Senior Vice President, Translational and Clinical Sciences, Oncology, at Regeneron (the developer of Libtayo). “This trial, which enrolled patients regardless of their PD-L1 status, demonstrated that Libtayo helped patients with recurrent or metastatic cervical cancer live longer after progression on prior chemotherapy. This is the fourth patient population in which Libtayo has shown clinical benefit and we look forward to submitting the results to regulatory authorities later this year.”